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Deep Phenotyping in KCNV2-associated Retinopathy

Cabral De Guimarães, Thales Antônio; (2023) Deep Phenotyping in KCNV2-associated Retinopathy. Doctoral thesis (PhD), UCL (University College London). Green open access

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KCNV2-associated retinopathy is an autosomal recessive cone-rod dystrophy with abnormal photopic responses associated with 'supernormal' and delayed rod ERG b-waves. Patients have reductions in cone-mediated vision including photophobia, with some experiencing nyctalopia, and progression over time. There are currently no treatments for KCNV2-associated retinopathy. However, there is a limiting lack of robust long term natural history data in large genetically proven groups of patients with the disease. These data are needed to be able to design clinical trials of future gene replacement therapy - and also to be able to provide more informed advice on prognosis and facilitate genetic counselling. I prospectively investigated and performed in depth clinical phenotyping of the condition with cutting-edge technology, including custom-built adaptive optics scanning laser ophthalmoscopy (AOSLO) and advanced analysis of retinal sensitivity measures to topographically model visual field data from the microperimetry. Our data suggests wide window of structural and functional preservation with an overall stable natural history. The genotype-phenotype analysis performed herein suggests a relatively milder disease course in patients with two missense variants, as opposed to loss-of-function mutations. Furthermore, we have identified the first hypomorphic allele in KCNV2, which was previously classified as benign, and we provide clinical and molecular evidence towards the reclassification of this variant.

Type: Thesis (Doctoral)
Qualification: PhD
Title: Deep Phenotyping in KCNV2-associated Retinopathy
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: CC BY-NC: Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
Keywords: KCNV2, Cone rod dystrophy, IRD, Inherited retinal dystrophy, Potassium channel, Kv8.2, Cone dystrophy with supernormal rod response, Retinal dystrophy, Endpoints, Natural history, Gene therapy, OCT, FAF, Genotype, Phenotype
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10179194
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